Careful monitoring still needed for patients with undetectable HIV while CD4s remain below 200

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Patients whose CD4 cell count does not recover despite achieving virologic control with HIV therapy require continued medical attention, results of a large European study presented to the recent International AIDS Society conference in Rome show.

Researchers found that individuals whose CD4 count failed to increase above 200 cells/mm3 were significantly more likely to experience a new AIDS-defining event or die than patients with more robust CD4 cell count increases.

“In virologically suppressed patients, lack of increase in CD4 cell count is relevant for prognosis and poorer outcome,” comment the investigators.



The prospect of survival and/or recovery from a disease as anticipated from the usual course of that disease or indicated by the characteristics of the patient.

virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

observational study

A study design in which patients receive routine clinical care and researchers record the outcome. Observational studies can provide useful information but are considered less reliable than experimental studies such as randomised controlled trials. Some examples of observational studies are cohort studies and case-control studies.

AIDS defining condition

Any HIV-related illness included in the list of diagnostic criteria for AIDS, which in the presence of HIV infection result in an AIDS diagnosis. They include opportunistic infections and cancers that are life-threatening in a person with HIV.

virologic response

Reduction in viral replication in response to treatment, especially achievement of an undetectable viral load.


Encouragingly, the research also suggested that patients whose CD4 cell count increases to above 500 cells/mm3 have an excellent long-term prognosis.

Modern HIV therapy is potent, easy to take and generally causes only mild side-effects. The goal of treatment is suppression of viral load below 50 copies/ml, and over 90% of patients can achieve this outcome within a year of starting antiretroviral treatment.

In most patients, suppression of viral load is accompanied by a gradual increase in CD4 cell count. Long-term HIV therapy can result in the restoration of CD4 cell count to normal levels.

However, despite having a successful virologic response to treatment, CD4 cell count fails to increase in some patients.

Investigators from the Collaboration of Observational HIV Epidemiology in Europe (COHERE) wished to determine the prognostic implications of poorer CD4 cell increases in patients whose viral load was suppressed.

A total of 66,147 individuals were included in their research. All experienced a fall in their viral load to undetectable levels after starting antiretroviral therapy. Their average age was 37 years, 73% were men, 26% had a prior AIDS diagnosis and 14% had a history of injecting drug use.

Median CD4 cell count at the time HIV therapy was started was high – 396 cells/mm3, and the patients had a baseline viral load of 4.6 log10 copies/ml.

When viral load was first suppressed below 50 copies/ml, 34% of patients had a CD4 cell count above 500 cells/mm3, 25% had a count between 350-500 cells/mm3, 26% a count of between 200-350 cells/mm3, and 16% had a CD4 cell count below 200 cells/mm3, including 1% with a count beneath the dangerously low level of 50 cells/mm3 – a well factor associated with a poor prognosis.

There were few new AIDS event or deaths among patients whose CD4 cell count was above 500 cells/mm3 (5 per 1000 patient years).

Events were also rare for patients in the 350-500 cells/mm3 and 200-350 cells/mm3 strata (7.9 and 12.0 per 1000 patient years respectively).

However, incidence was markedly higher for patients with a CD4 cell count below 200 cells/mm3 (30.5 per 1000 patient years), especially so for those with a CD4 cell count beneath 50 cells/mm3 (94.9 per 1000 patient years).

The investigators plotted the impact of CD4 cell count on long-term outcomes.

The prognosis for patients with virologic suppression and a CD4 cell count above 500 cells/mm3 was excellent. The investigators calculated that they had a 95% probability of survival/avoidance of AIDS.

Projected outcome for patients with a well-controlled viral load and CD4 cell counts between 500-350 or 200-350 cells/mm3 were also good, with event-free survival projected for approximately 90%.

However, at lower CD4 cell counts the chance of remaining alive and AIDS free were significantly poorer. The projected event-free survival rate for patients with a CD4 cell count beneath 200 cells/mm3 was in the region of 65%.

There was also robust evidence that the time to an event was significantly shorter for patients whose CD4 cell count did not increase above 200 cells/mm3 despite virological suppression (HR = 0.21, 95% CI, 0.19-0.24 vs. HR = 0.92, 95% 0.90-0.94 for patients with a CD4 cell count above 200 cells/mm3).

“In virologically suppressed patients an increase in CD4 cells reduces the risk of AIDS or death,” comment the investigators, “lack of increase in CD4 cell is relevant for prognosis and poorer outcome.”


Bucher HC et al. Risk of progression to AIDS or death in relation to CD4 cell levels in HIV-infected patients with sustained viral response to cART. Sixth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Rome, abstract WELBB01, 2011.

View this abstract on the conference website.